Macrocyclic lactones, and in particular, the “azalides” are semi-synthetic compounds with a range of biological activities. Amongst the best known of these is antibiotic activity through binding to the bacterial ribosome. The compounds do, however, have a range of other activities including anti-inflammatory activity (see, e.g., EP0283055). In recent years, it has been proposed that macrocycles may have broader application as drug carriers in which an active substance is reversibly bonded to the macrocycle via an ester bond (see, e.g., PCT 03/070174).
Various observations have linked the anti-bacterial activity of macrolides to the interaction between the hydroxyl group on the desosamine ring and the bacterial ribosome. Modification of this position on the macrolide, should, therefore, reduce anti-biotic activity while providing for alternative interactions with other target proteins.
A large number of researchers have reported derivatives with variation in this part of the molecule including Kobrehel et al. Also reported are substitutions on the macrolactone ring or modification of the sugar residues (for example, cladinose to carbonyl in the case of the ketolides). However, the majority of this work has been performed with the objective of designing new molecules having antibiotic activity.